Method and apparatus for processing a lumen device

ABSTRACT

A device and method provide an aerosol germicide to a device having a lumen within a container. The container is divided into at least two compartments by an interface across which extends the lumen device, with one end of the lumen in one compartment and another end of the lumen in another compartment. A pressure differential can be used to flow the germicide through the lumen.

[0001] This application is a continuation-in-part of application Ser.No. 09/323,610, filed Jun. 1, 1999, which is a continuation ofapplication Ser. No. 08/915,922, filed Aug. 21, 1997, now U.S. Pat. No.6,066,294, the entire contents each of which are hereby incorporatedherein by reference.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The invention relates to systems used for chemical sterilizationof medical devices, and more particularly, to systems having multiplechambers used for chemical sterilization of medical devices.

[0004] 2. Description of the Related Art

[0005] Medical instruments have traditionally been sterilized usingeither heat, such as is provided by steam, or a chemical, in the gas orvapor state. Sterilization using hydrogen peroxide vapor has been shownto have some advantages over other chemical sterilization processes.

[0006] The combination of hydrogen peroxide with a plasma providescertain additional advantages, as disclosed in U.S. Pat. No. 4,643,876,issued Feb. 17, 1987 to Jacobs et al. U.S. Pat. No. 4,756,882, issuedJul. 12, 1988 also to Jacobs et al. discloses the use of hydrogenperoxide vapor, generated from an aqueous solution of hydrogen peroxide,as a precursor of the reactive species generated by a plasma generator.The combination of hydrogen peroxide vapor diffusing into closeproximity with the article to be sterilized and plasma acts to sterilizethe articles and remove residual hydrogen peroxide. However, effectivesterilization of articles having long narrow lumens are very difficultto achieve, since the methods are dependent upon diffusion of thesterilant vapor into close proximity with the article beforesterilization can be achieved. Thus, these methods have been found torequire high concentration of sterilant, extended exposure time and/orelevated temperatures when used on long, narrow lumens. For example,lumens longer than 27 cm and/or having an internal diameter of less than0.3 cm have been particularly difficult to sterilize. The sterilizationof articles containing long narrow lumens therefore presents a specialchallenge.

[0007] U.S. Pat. No. 4,744,951 to Cummings et al. discloses atwo-chambered system which provides hydrogen peroxide in vapor form foruse in sterilization processes. The sterilant is initially vaporized inone chamber and then applied to the object to be sanitized in anothersingle sterilizing chamber, thereby producing a concentrated hydrogenperoxide vapor which is relatively more effective. The sterilizationprocesses are designed for furnishing concentrated hydrogen peroxidevapor to interior surfaces of articles having a tortuous or a narrowpath. However, the sterilization processes are ineffective at rapidlysterilizing lumened devices, since they depend on the diffusion of thehydrogen peroxide vapor into the lumen to effect sterilization.

[0008] U.S. Pat. No. 4,797,255 to Hatanaka et al. discloses atwo-chambered sterilization and filling system consisting of a singlesterilization chamber adjacent to a germ-free chamber utilized fordrying and filling sterilized containers.

[0009] U.S. Pat. No. 4,863,688 to Schmidt et al. discloses asterilization system consisting of a liquid hydrogen peroxidevaporization chamber and an enclosure for sterilization. The enclosureadditionally may hold containers wherein the hydrogen peroxide sterilantvapor does not contact the interior of the containers. This system isdesigned for controlling the exposure to the hydrogen peroxide vapor.The system is not designed for sterilizing a lumen device.

[0010] U.S. Pat. No. 4,952,370 to Cummings et al. discloses asterilization process wherein aqueous hydrogen peroxide vapor is firstcondensed on the article to be sterilized, and then a source of vacuumis applied to the sterilization chamber to evaporate the water andhydrogen peroxide from the article. This method is suitable to sterilizesurfaces, however, it is ineffective at rapidly sterilizing lumeneddevices, since it too depends on the diffusion of the hydrogen peroxidevapor into the lumen to effect sterilization.

[0011] U.S. Pat. No. 4,943,414, entitled “Method for Vapor Sterilizationof Articles Having Lumens,” and issued to Jacobs et al., discloses aprocess in which a vessel containing a small amount of a vaporizableliquid sterilant solution is attached to a lumen, and the sterilantvaporizes and flows directly into the lumen of the article as thepressure is reduced during the sterilization cycle. This system has theadvantage that the water and hydrogen peroxide vapor are pulled throughthe lumen by the pressure differential that exists, increasing thesterilization rate for lumens, but it has the disadvantage that thevessel needs to be attached to each lumen to be sterilized.

[0012] U.S. Pat. Nos. 4,937,046, 5,118,471 and 5,227,132 to Anderson etal. each disclose a sterilization system which uses ethylene oxide gasfor sanitation purposes. The gas is initially in a small first enclosureand thereafter slowly permeates into a second enclosure where theobjects to be sterilized are located. A medium is then introduced intothe second enclosure to flush out the sterilizing gas into a thirdenclosure containing the second enclosure. An exhaust system thenexhausts the sterilant gas and air from the third enclosure. Thesesystems also have the disadvantage of relying on the diffusion of thesterilant vapor to effect sterilization and hence are not suitable forrapidly sterilizing lumened devices.

[0013] U.S. Pat. No. 5,122,344 to Schmoegner discloses a chemicalsterilizer system for sterilizing items by vaporizing a liquid chemicalsterilant in a sterilizing chamber. Pre-evacuation of the sterilizerchamber enhances the sterilizing activity. Sterilant is injected intothe sterilizer chamber from a second prefilled shot chamber. This systemalso relies upon diffusion of sterilant vapor to effect sterilizationand is also not suitable for rapidly sterilizing lumened devices.

[0014] U.S. Pat. No. 5,266,275 to Faddis discloses a sterilizationsystem for disinfecting instruments. The sterilization system contains aprimary sterilization chamber and a secondary safety chamber. Thesecondary safety chamber provides for sensing and venting to adestruction chamber any sterilization agent that is released from theprimary sterilization chamber. This system, as in other systems, alsorelies upon diffusion of sterilant vapor to effect sterilization and isalso not suitable for rapidly sterilizing lumened devices.

[0015] In U.S. Pat. Nos. 5,492,672 and 5,556,607 to Childers et al,there is disclosed a process and apparatus respectively for sterilizingnarrow lumens. This process and apparatus uses a multicomponentsterilant vapor and requires successive alternating periods of flow ofsterilant vapor and discontinuance of such flow. A complex apparatus isused to accomplish the method. Additionally, the process and apparatusof '672 and '607 require maintaining the pressure in the sterilizationchamber at a predetermined subatmospheric pressure.

[0016] In U.S. Pat. No. 5,527,508 to Childers et al., a method ofenhancing the penetration of low vapor pressure chemical vaporsterilants into the apertures and openings of complex objects isdisclosed. The method repeatedly introduces air or an inert gas into theclosed sterilization chamber in an amount effective to raise thepressure to a subatmospheric pressure to drive the diffused sterilantvapor further into the article to achieve sterilization. The '508, '672and '607 Childers inventions are similar in that all three requirerepeated pulsations of sterilant vapor flow and maintenance of thesterilization chamber pressure at a predetermined subatmosphericpressure.

[0017] In U.S. Pat. No. 5,534,221 to Hillebrenner et al., a device andmethod for sterilizing and storing an endoscope or other lumened medicaldevice is disclosed. The device includes a sealable cassette in whichthe endoscope or other medical device is placed. The cassette has aninput port for receiving a sterilizing agent through a connector, anoutput port for expelling the sterilizing agent when a vacuum is appliedthereto through a connector, and check valves in the input and outputports to open the ports when the connectors are coupled to the ports andto seal the ports when the connectors are removed from the ports suchthat after the endoscope has been sterilized, it remains sterilizedwithin the cassette until the cassette is opened. The method of the '221invention involves placing the medical device inside the cassette andcoupling the device to either the input or output port of the cassette.The cassette is then placed in an outer oven-like container or warmingchamber where the temperature is properly maintained. Connections aremade to open the input and output ports on the cassette such that thesterilizing agent may be introduced through a first port to bathe theoutside of the medical instrument or other object, such as an endoscopewhile one end of the hollow object, such as the endoscope, is coupled tothe output port where a vacuum is supplied external to the cassette topull the sterilization agent into the cassette and through the interiorpassageways of the endoscope. When the sterilization process iscompleted, the warming chamber is opened and the sterilizing cassette issimply removed from the chamber with the input and output ports beinguncoupled from their respective sources. A tight seal is maintained andthe object remains in the sterilized interior of the cassette until thecassette is opened or the device is to be used. Thus, the '221 inventionis concerned with providing a means whereby a sterilized medical devicecan be retained within a cassette in which it was sterilized until readyfor use, thus avoiding any contamination by exposure to the atmosphereor handling before use. Additionally, in some cases of the '221invention, wherein the lumen of the device to be sterilized is connectedto the output port, particularly wherein the devices have long, narrowlumens, the time to expel the sterilizing agent through the lumen andout of the cassette may be undesirably long. Also, in cases wherein thelumen device is very flexible, lumen collapse may occur, either slowingor preventing vapor exit or causing lumen damage.

[0018] U.S. Pat. Nos. 5,445,792 and 5,508,009 to Rickloff et al. eachdisclose a sterilization system essentially equivalent to the systemdisclosed in Hillebrenner '221.

[0019] U.S. Pat. No. 5,443,801 to Langford teaches a transportablecleaning/sterilizing apparatus and a method for inside-outsidesterilization of medical/dental instruments. The apparatus avoids theuse of heat, pressure, severe agitation, or corrosive chemicals whichmight damage delicate equipment. This invention uses ozone gas orsolution as sterilant. It does not involve the use of sterilant vapor orvaporizing a sterilant solution into vapor, and is not suitable foroperations under vacuum because flexible bags or containers are used.

[0020] In consideration of the foregoing, no simple, safe, effectivemethod of sterilizing smaller lumens exists in the prior art. Thus,there remains a need for a simple and effective method of vaporsterilization of articles with both long, narrow lumens as well asshorter, wider lumens. Furthermore, there also remains a need for asimple and effective sterilization system with independently operablechambers.

SUMMARY OF THE INVENTION

[0021] The present invention provides an apparatus for treating a lumendevice which has a lumen therethrough, the lumen having a first end anda second end. The apparatus comprises a container with at least oneinterface which separates the container into at least a firstcompartment and a second compartment. The interface has an openingtherethrough to receive the lumen device with the first end of the lumenin the first compartment and the second end of the lumen in the secondcompartment. A source of germicide is in fluid communication with thecontainer, and the germicide is in aerosol form.

[0022] Preferably, the apparatus further comprises some means forcreating a pressure differential between the first chamber and thesecond chamber whereby to induce a flow of the germicide from the firstchamber toward the second chamber through the lumen. Such means maycomprise, for instance, a vacuum pump connected to the second chamber,or a pump connected to the first chamber and to the second chamber.

[0023] Preferably, the germicide comprises hydrogen peroxide.

[0024] Preferably, the interface is adapted to seal around the lumendevice.

[0025] A method is provided according to the present invention fortreating a lumen device, the lumen device having a lumen therethrough,and the lumen having a first end and a second end. The method comprisesthe steps of: providing a container with at least one interface, whereinthe at least one interface separates the container into at least a firstcompartment and a second compartment; placing the lumen device incontainer extending across the at least one interface, wherein the firstend is in the first compartment and the second end is in the secondcompartment; and introducing a germicide in aerosol form into the firstcompartment; and flowing the germicide from the first compartmentthrough the lumen into the second compartment.

[0026] Preferably, the germicide is flowed from the first chamber towardthe second chamber through the lumen by creating a pressure differentialbetween the first chamber and the second chamber. In one embodiment, thepressure differential between the first chamber and the second chamberis created by lowering the pressure in the second chamber with a vacuumpump. In another embodiment, the pressure differential between the firstchamber and the second chamber is created by pumping atmosphere from thesecond chamber into the first chamber.

[0027] Preferably, the method further comprises the step of sealing theinterface around the lumen device.

BRIEF DESCRIPTION OF THE DRAWINGS

[0028]FIG. 1 is a schematic diagram of an embodiment of the apparatus ofthe present invention showing two chambers separated with a sealableinterface;

[0029]FIG. 1A is a schematic diagram of an embodiment of the apparatusof the present invention showing the interface, doors and two chambers;

[0030]FIG. 2 is a schematic diagram of an embodiment of the apparatus ofthe present invention showing two chambers separated by an interface andin fluid communication through a lumen device;

[0031]FIG. 3 is a schematic diagram of an embodiment of the apparatus ofthe present invention showing one chamber placed in another chamber;

[0032]FIG. 4 is a schematic diagram of an embodiment of the apparatus ofthe present invention showing one chamber in another with lumenconnecting the two chambers;

[0033]FIG. 5 is a schematic diagram of an embodiment of the apparatus ofthe present invention showing two chambers containing containers;

[0034]FIG. 6B is a schematic diagram of an embodiment of the apparatusof the present invention showing two chambers containing containers andbeing connected through a lumen;

[0035]FIG. 6A is a cross sectional view of the system of FIG. 6B;

[0036]FIG. 7 is a schematic diagram of an embodiment of the apparatus ofthe present invention showing a container in the chambers separated withan interface.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0037] The multi-compartment sterilization apparatus of the presentinvention is suitable for the sterilization of both non-lumen and lumendevices.

[0038] According to one aspect of the present invention, themulti-compartment sterilization apparatus comprises at least twochambers separated by a sealable and removable interface. Each of thechambers can be operated independently and serve as a sterilizationchamber. In a sterilization process using the apparatus of the presentinvention, the interface can be adjusted for different situations. Forexample, if the device to be sterilized is too big to fit into neitherone of the two chambers, the interface can be removed so that more spacewill be available to accommodate the device. If the device is not sobig, it can be sterilized in one of the two chambers while other devicescan be prepared for sterilization in the other chamber.

[0039] According to another aspect of the present invention, themulti-compartment sterilization apparatus comprises a sterilizationsystem with a multi-chambered compartment having at least a first rigidchamber and a second rigid chamber, an openable and closeable interfacebetween the first and second chamber, a flow path between the first andsecond chamber, and a source of sterilant adapted to provide thesterilant in the first and/or second chamber. The flow path can be alumen of the device to be sterilized, so that sterilant can flowdirectly through the lumen to sterilize the interior of the lumendevice. Different sterilization methods and technologies can be used incorporation with the sterilization system of the present invention.Several embodiments of those methods are described below:

Method to Deliver a Predetermined Amount of Liquid Sterilant

[0040] Conventional sterilants can be used in the present invention.Numerous sterilants are available in the art, such as formaldehyde,ethylene oxide, hydrogen peroxide solution and hydrogen peroxide vapor.Although any of those sterilants can be used in the sterilizationapparatus of the present invention, the use of hydrogen peroxidesolution and hydrogen peroxide vapor has been shown to have someadvantages over other chemical sterilization processes. Therefore, it ispreferred to use hydrogen peroxide solution and hydrogen peroxide vaporas sterilant in the present invention. In a sterilization process usinghydrogen peroxide solution as sterilant, the sterilant can be applied inseveral different ways. For example, a hydrogen peroxide solution can befirst vaporized under vacuum and/or heat in a vacuum chamber, and thedevice to be sterilized is then exposed to the hydrogen, peroxide vapor.Accordingly, in one embodiment of the present invention, an importantparameter of the process needed to achieve satisfactory sterilization isthe amount of liquid hydrogen peroxide entering into the chamber to bevaporized. Thus, it is important that the liquid hydrogen peroxide bedelivered to the chamber in measured quantities.

[0041] A sterilization apparatus able to deliver a predetermined amountof liquid sterilant can be incorporated into the sterilization system ofthe present invention. Thus, the sterilization chamber may have a bottomwall with at least one well which defines a known volume. The well ispositioned so that when a liquid sterilant is introduced onto the bottomsurface, a known volume of the liquid sterilant fills the well and whenthe liquid sterilant is drained from the surface, the known volume ofliquid sterilant remains in the well so that a subsequent sterilizationprocess can be performed on the device positioned on the bottom surfacewith the known volume of liquid sterilant positioned within the bottomsurface. The apparatus may also include a heat source and/or a vacuumsource for vaporizing the liquid sterilant in the well, and canoptionally include a source of plasma. The bottom surface preferably hasat least one perforation for draining the liquid sterilant from thebottom surface. The well formed in the bottom surface can be curved,flat or angled. Thus, the well can be an inwardly extendinghemispherical projection. The well can also be formed in the bottomsurface as an inwardly extending rectangular projection having roundedends. The well formed in the bottom surface can also be a rectangularbox having side walls, defining an opening. Where perforations areprovided, they can be disposed adjacent the well, and can be roughlyspherical in shape. The upwardly extending projection can include aperforation thereon, which can be on top of the projection or on a sideof the, projection. The bottom surface can be a sloped surface, a convexor concave surface or a V-shaped surface. The bottom surface can be of avariety of materials including stainless steels, aluminum, aluminumalloys, liquid crystal polymers, polyesters, polyolefin polymers orfluorinated polyolefins. If the bottom surface is comprised of acomposite material, the composite material can include a filler of highthermal conductivity. Examples of composite materials include ametal-filled polymer, a ceramic-filled polymer and a glass-filledpolymer. Those materials are also suitable for the side walls and doorsof the sterilization chamber.

Method Based on Diffusion Restricted Environments

[0042] A method of hydrogen peroxide vapor sterilization ofdiffusion-restricted environments can also be used in corporation withthe present invention. In this embodiment of the present invention, thedevices (lumen or non-lumen) to be sterilized are pretreated with ahydrogen peroxide solution, and then exposed to pressures less than thevapor pressure of sterilant. The inside of lumens is sterilized bytaking advantage of the diffusion-restricted environments within thelumens.

[0043] As used herein, a “diffusion-restricted” area refers to any oneor more of the following properties: (1) the ability of the area of anarticle placed within the sterilization system of the present inventionto retain 0.17 mg/L or more hydrogen peroxide solution after one hour at40° C. and 10 torr; (2) having the same or more diffusion restrictionthan provided by a single entry/exit port of 9 mm or less in internaldiameter and 1 cm or greater in length; (3) having the same or morediffusion restriction than provided by a lumen 27 cm in length andhaving an internal diameter of 3 mm; (4) having the same or morediffusion restriction than provided by a lumen having a ratio of lengthto internal diameter greater than 50; (5) the ability of an articleplaced within the sterilization system of the present invention toretain 17% or more of the hydrogen peroxide solution placed thereinafter one hour at 40° C. and 10 torr; or (6) being sufficientlydiffusion-restricted to completely sterilize a stainless steel bladewithin a 2.2 cm by 60 cm glass tube having a rubber stopper with a 1 mmby 50 cm stainless steel exit tube therein at a vacuum of 10 torr forone hour at 40° C. in accordance with the present invention. It isacknowledged that characteristics (1) and (5) will vary depending on theinitial concentration of hydrogen peroxide placed into the article;however, this can be readily determined by one having ordinary skill inthe art.

[0044] In this embodiment of the present invention, a method forsterilizing an interior of a device with a diffusion restricted area,such as a device having a lumen, is used in corporation with thesterilization system. The method includes the steps of contacting theinterior of the device with a liquid solution comprising hydrogenperoxide, and exposing the device to negative pressure for a time periodsufficient to effect complete sterilization. In one embodiment, theliquid solution is peracetic acid. If the exposing step is conducted for1 hour at 40° C. and 10 torr, the diffusion restricted area preferablyretains 0.17 mg/L or more hydrogen peroxide, or retains 17% or more ofthe hydrogen peroxide placed therein after the exposing step. In certainpreferred embodiments, the diffusion-restricted area has the same ormore diffusion restriction than provided by a lumen 27 cm in length andan internal diameter of 3 mm, or has the same or more diffusionrestriction than provided by a lumen having a ratio of length tointernal diameter greater than 50. The solution is preferably at aconcentration of less than 25% by weight. The contacting step can beperformed by delivery via a method such as injection, static soak,liquid flowthrough or aerosol spray. In a preferred embodiment, thediffusion-restricted area is a lumen at least 27 cm in length and havingan internal diameter of no more than 3 mm, more preferably having aninternal diameter of no more than 1 mm. The exposing step is preferablyperformed for 60 minutes or less, and is preferably performed at apressure less than the vapor pressure of hydrogen peroxide. Thus, thepreferred pressure range under conditions of the present invention isbetween 0 and 100 torr. In one particularly preferred embodiment, thepressure is approximately 10 torr and the exposing step is conducted ata temperature of approximately 23° C. to approximately 28° C. Theexposing step can include the step of heating the article, such as byheating the chamber in which the exposing step occurs. The chamber canbe heated to about 30° C. to about 45° C. Alternatively, the solutioncan be heated, such as to a temperature of about 30° C. to about 45° C.Optionally, the step of exposing the device to a plasma can be conductedduring the step of exposing the device to negative pressure. In oneembodiment employing exposure to plasma, the method is performed withina first chamber and the plasma is generated in a second, separatechamber. This embodiment further comprises the step of flowing theplasma into the first chamber. Advantageously, the contacting and/orexposing steps of the method can be repeated one or more times.

Sterilization Methods in Non-diffusion Restricted Environments

[0045] The present invention can also be used to sterilize devices withlumens without relying on a diffusion-restricted environment.

[0046] It has been discovered by the inventors that similarsterilization results to those created in diffusion-restrictedenvironments can be created through controlling the evacuation rate ofthe chamber in which articles to be sterilized are placed. Thus, in oneembodiment of the present invention, a method for sterilizing a devicecan be used in corporation with the sterilization system of the presentinvention. The method comprises the steps of contacting the device withliquid sterilant outside or inside a sterilization chamber at a firstpressure; placing the device in the chamber before or after thecontacting step; and decreasing the pressure of the chamber to a secondpressure below the vapor pressure of the liquid sterilant in which atleast a portion of the decrease in pressure below about the vaporpressure of the liquid sterilant occurs at a pumpdown rate of less than0.8 liters per second, calculated based on the time required to evacuatethe chamber from atmospheric pressure to 20 torr when the chamber isempty and dry, i.e. when the chamber has neither articles to besterilized nor a visible quantity of liquid within it. According to oneaspect of this preferred embodiment, at least the decrease in pressurebelow about two times the vapor pressure of the liquid sterilant occursat a pumpdown rate of less than 0.8 liters per second. According toanother aspect of this embodiment, the decrease in pressure below aboutfour times the vapor pressure of the liquid sterilant occurs at apumpdown rate of less than 0.8 liters per second. Preferably, thepumpdown rate is 0.6 liters per second or less; more preferably, 0.4liters per second or less; and most preferably, 0.2 liters per second orless. Advantageously, the first pressure is atmospheric pressure.Preferably, the liquid sterilant is hydrogen peroxide. In anotheraspect, the device is a medical instrument having a lumen.

[0047] The present invention can also use a method for sterilizing adevice comprising the steps of (a) contacting the device with liquidsterilant outside or inside a sterilization chamber at a first pressure;(b) placing the device in the chamber before or after the contactingstep; (c) pumping down the chamber to a second pressure which is lowerthan the first pressure at a first rate; and (d) pumping down thechamber to a third pressure which is lower than the second pressure,wherein at least a portion of the pumping down to the third pressure isat a second rate which is slower than the first rate. The pumpdown rateeither above and/or below the second pressure can be constant orvariable. I n certain embodiments, the pumpdown rate either above and/orbelow the second pressure is reduced in stepwise fashion. Preferably,the second pressure is greater than or equal to about the vapor pressureof the liquid sterilant; more preferably, the second pressure is greaterthan or equal to about two times the vapor pressure of the liquidsterilant; most preferably, the second pressure is greater than or equalto about four times the vapor pressure of the liquid sterilant.Advantageously, the pumpdown rate in step (d) is 0.8 liters/sec or less;more advantageously 0.6 liters/sec or less; even more advantageously 0.4liters/sec or less; and most advantageously 0.2 liters/sec or less,calculated based on the time required to evaluate the chamber fromatmospheric pressure to 20 torr under empty and dry conditions.Preferably, the liquid sterilant is hydrogen peroxide. In another aspectof this embodiment, the device is a medical instrument having a lumen.Preferably, the pumping down of step (c) reduces the pressure to lessthan about three times, more preferably to less than about two times,the vapor pressure of the liquid sterilant.

[0048] Another suitable method includes contacting the article withliquid sterilant either inside or outside of the sterilization chamber,placing the device in the chamber either before or after the contactingstep, and reducing the pressure of the chamber while regulating thepumpdown rate so as to control the evaporation rate of sterilant in saidchamber. In any of the methods described above, the contacting step maycomprise application of liquid or condensed vapor. These methodsdescribed above may additionally comprise further evacuating the chamberto remove residual sterilant. Further, these methods described above mayadditionally comprise exposing the device to plasma to remove residualsterilant or enhance sterilization efficacy. The contacting step inthese methods can be either by direct or indirect contacting. As statedhereinbelow, indirect contacting involves introducing sterilant into thechamber without directly contacting the article to be sterilized.

[0049] In another embodiment, a two step pump down sterilization processcan be used in connection with the sterilization system of the presentinvention. The method comprises the steps of: contacting a device withliquid sterilant outside or inside a sterilization chamber; placing thedevice in the chamber before or after the contacting step; bringing thepressure of the chamber to a first pressure range at which liquidsterilant is vaporized from the non-diffusion restricted area tosterilize the non-diffusion restricted area; bringing the pressure ofthe chamber to a second pressure range at which the liquid sterilant isvaporized from the diffusion restricted area to sterilize the diffusionrestricted area, wherein the minimum pressure in the second pressurerange is lower than the maximum pressure in the first pressure range.

[0050] Preferably, the first pressure range is 20 to 760 torr; morepreferably, the first pressure range is 20 to 80 torr; most preferably,the first pressure range is 40-50 torr. Advantageously, the secondpressure range is 1-30 torr; more advantageously, the second pressurerange is 5-10 torr. In one aspect of this preferred embodiment, thedevice includes a diffusion-restricted environment. Preferably, thedevice is a medical instrument with a lumen having an interior and anexterior surface. Advantageously, the sterilant is hydrogen peroxide.According to another aspect of this preferred embodiment, the chamber isat a set temperature and wherein the first pressure is greater than thevapor pressure of the sterilant at the set temperature. Preferably, thepressure of the chamber is maintained constant at the first pressure fora time period sufficient to sterilize the non-diffusion restricted area.Advantageously, the pressure of the chamber is maintained constant atthe second pressure for a time period sufficient to sterilize thediffusion restricted area. The pressure of the chamber may be permittedto increase after reaching the first or second pressure range as aresult of vaporization of the sterilant within said chamber.Alternatively, the pressure of the chamber is permitted to decreaseafter reaching the first or second pressure through pumping of saidchamber at a rate slower than used to decrease the pressure between saidfirst and second pressure ranges. Preferably, the contacting step iswith liquid or condensed vapor. The method can also include the steps ofbringing the pressure to a third pressure lower then the second pressureto remove residual sterilant and/or exposing the device to plasma toremove residual sterilant or enhance sterilization efficacy.

Method Involving Direct Flow Through A Lumen Of Devices To Be Sterilized

[0051] According to the present invention, a sterilization apparatus isprovided which can more efficiently sterilize devices with long narrowlumens by flowing a sterilant, either in liquid phase or in vapor phase,directly through the lumens of lumen devices to be sterilized.

[0052] The flow of a sterilant (solution or vapor) through a lumen of amedical device is realized by a pressure drop between two ends of thelumen. The pressure drop can be generated by applying either a vacuum ora high pressure at one end. By generating a forced flow through apressure differential other than relying on diffusion, the sterilizationrate is significantly increased and less time is needed for asterilization cycle.

[0053] It is clear from the above discussion that the two ends of thelumen need to be exposed to a pressure differential. This is achieved inthe present invention by placing a sealable interface between the twochambers. An opening is provided in the interface and the lumen deviceto be sterilized is placed through the opening in such a way that thelumen serves as a flow path between the two chambers.

[0054] The opening can be constructed in several ways. One way toachieve this is with a camera shutter approach employing an irisdiaphragm, such as a precision iris diaphragm from Edmund Scientific. Anoptional spring can be used to secure the closure of the shutter.Another way to achieve an acceptable opening is to employ two plates,wherein the area between the two plates has a compressible material,such as a rubber material. The lumen device can be placed between thetwo plates and the two plates moved together to form a gas and vaporimpermeable seal around the lumen device. Optionally, a porous materiallike a sponge or air permeable material may be utilized for thecompressible material. In this case some sterilant can flow between thecompressible material and the lumen device. However, most the sterilantflows through the lumen device. Yet another acceptable interface is ahole or horizontal opening for one or more lumen devices, said hole oropening being a gas or liquid inflatable so that by inflating theinflatable material on the hole or opening the lumen devices are heldand sealed. Still another option is to place a compressible material ontop of an inflatable material so as to facilitate the sealing around thelumen device.

[0055] The closing and opening movement of the opening such as the plateand the iris diaphragm can be controlled mechanically or electronicallywith any conventional mechanism.

[0056] It is sealed to a different degree between the opening and thelumen device depending on the desired purpose. For example, the openingcan form a gas-tight seal around the lumen device so that nothing canflow outside of the lumen device through the opening; or form aloose-fitting seal around the lumen device allowing sterilant to flowoutside of the lumen device through the opening so that the exterior ofthe lumen device adjacent the opening can be sterilized; or form atight-fitting with a porous material, such as a gas and/or liquidpermeable membrane around the lumen device so that gas and sterilant canpass and, in the meantime, the porous material helps to hold the lumendevice. The interface can be made openable, closeable, and removable. Aflow path between different chambers can be also provided outside thesterilization system.

[0057] In order to promote sterilization efficiency, all thesterilization apparatus of the present invention can be further equippedwith a heater, vacuum, and/or a plasma.

[0058] The present invention is further described in connection with thedrawings below. In the following figures like numbers refer to likeparts throughout. Referring to FIG. 1, the sterilization apparatuscomprises a first chamber 2 and a second chamber 4. The two chambers areseparated by a sealable and removable interface 6 so that the twochambers can be operated independently, i.e. different items can besterilized simultaneously in the two chambers, or one chamber isoperated for sterilization while the other is not in operation. Anenclosure 10 for receiving a sterilant source 12 is connected to each ofchambers 4 and 2 through a valve 14 a and a valve 14 b, respectively.Two enclosures 10 are shown in FIG. 1. However, these two enclosures 10can be combined into one. Enclosure 10 can be made of materials similarto those of the walls of chambers 2 and 4. The sterilant source 12 canbe located in one or more locations of enclosure 10, chamber 2, and/orchamber 4. There are several way to control the amount of sterilantentering chamber 2 or 4 if such control is desired. For example, valves14 a and 14 b can be a metering valve and the amount of sterilantflowing from enclosure 10 to chambers 2 and 4 is measured and controlledby valve 14 a or 14 b; or enclosure 10 is equipped with a volume readingso that the volume of the sterilant in enclosure 10 can be read; orsterilant containing wells (not shown) can be provided in the chambersto control the amount of liquid sterilant. The sterilant source 12 canbe also located in chamber 2 and/or chamber 4.

[0059] Chambers 2 and 4 are equipped with a vacuum pump 16 forgenerating vacuum within these chambers during the sterilizationprocess. Valve 15 a and valve 15 b are provided connecting vacuum pump16 to chamber 4 and 2, respectively. They are controlled independently.Chambers 2 and 4 can also be equipped with a pump 18 to circulatesterilant between the two chambers. Chambers 2 and 4 can be of anydesired shape, but a regular shape such as cylindrical or rectangularwill make it easier to accommodate the interface 6.

[0060]FIG. 1A shows more details of chambers 2 and 4 with interface anddoors. As shown in this figure, chambers 2 and 4 can be equipped withdoors 8 a, 8 b, 9 a, and 9 b, respectively. One chamber does notnecessarily have more than one door. There are a frame 11 a and aguiding piece 11 b between the two chambers. Interface 6 a or 6 b issecured between the two chambers through frame 11 a and guiding piece 11b by sliding the interface into gap 13 defined by frame 11 a and guidingpiece 11 b. If necessary, interface 6 a or 6 b can be further secured toframe 11 a by any conventional means, such as screw or clamp. A sealingO-ring (not shown) can be provided around the frame 11 a to generate agood sealing between the two chambers. The interface 6 a has an opening7 adapted to receive a lumen device. Opening 7 may have different shapeand size to accommodate different types of lumen devices. Underdifferent situation, different interface can be chosen. The opening 7 iscontrollable. In one embodiment the opening has a shutter structurewhich is electrically controlled. By changing the dimension of theopening, different degree of seal between the opening and the lumendevice held by the opening can be achieved.

[0061]FIG. 2 shows a sterilization apparatus able to generate asterilant flow through a lumen to be sterilized. As shown in FIG. 2, theapparatus comprises a first chamber 2 and a second chamber 4. The twochambers are separated by an openable and closeable interface 6 a.Interface 6 a has an opening 7. A lumen device 40 with a lumen 42 isplaced through the opening 7 in such a way that one end of the lumen 42is in chamber 2 and the other end in chamber 4. At least during a partof a sterilization process for sterilizing the interior of the lumen 42,the opening 7 is gas-tight sealed around the lumen device 40 so thatsterilant fluid flows through the lumen 42 under a pressure drop betweenthe two chambers 2 and 4. Although a liquid sterilant can be used in theapparatus, sterilant vapor is preferred. The sterilant vapor can begenerated with any appropriate method known to the art or with themethod described in the copending application referenced previously.Generally speaking, the usual way to generate vapors in a sterilizationsystem is the use of heating and/or vacuum. In the present invention,both heating and vacuum can be employed to generate sterilant vapor.

[0062] In order to generate a flow of sterilant fluid through the lumen42, pressure differential has to be exist between the two ends of thelumen 42. One way of generating such a pressure gradient is topressurize one end of the lumen 42. But it is more desirable to applyvacuum to one end of the lumen 42 with vacuum pump 16, especially whensterilant vapor is used. The two chambers can be operated either undervacuum or under pressure up to about 4 atm. The temperature of the twochambers can be controlled independently through a conventional heatingdevice (not shown). The operation temperature of the chambers areadjusted so as not to damage the device to sterilized. It is usuallybelow 80 C., more preferably 20-55 C.

[0063] Vacuum pump 16 is used to generate vacuum in either chamber 2 orchamber 4 through valve 15 b and 15 a. Pump 18 is used to circulatesterilant between chamber 2 and chamber 4. If necessary, vacuum pump 16and air pump 18 can be operated either simultaneously or sequentially.

[0064] In addition to lumen device 40, a plurality of devices can besterilized in both chamber 2 and 4. In this embodiment, the devices tobe sterilized can be pretreated or not pretreated with liquid sterilant.Because sterilant is circulated through the lumen 42, the interior ofthe lumen device 40 is mainly sterilized by the sterilant flowtherethrough. This direct circulation of sterilant provides an efficientsterilization of the interior of the lumen 42, especially, when hydrogenperoxide vapor is circulated through the lumen 42. Doors can be providedfor the two chambers at any convenient locations, for example, as shownin FIG. 1A. Sterilant can be provided from enclosure 10, or directlyfrom the source of sterilant 12. The sterilant source 12 can be in theform injection, static soak, liquid flowthrough, or aerosol spray.Liquid sterilant may also be placed on the wells (not shown) on thebottom surface of the chambers and is vaporized during the sterilizationby applying vacuum and/or heating.

[0065] All the features and functions of the apparatus shown in FIG. 1and described previously are applicable to the apparatus shown in FIG.2.

[0066]FIG. 3 shows a top view of the two chambers in another embodimentof the present invention. The apparatus comprises similar elements asthat shown in FIG. 2, but they are configured differently. Chamber 4 isnow located inside chamber 2. Chambers 2 and 4 are still separatelyconnected to vacuum pump 16, enclosure 10, and pump 18 as shown in FIG.3. Pump 18 usually is not needed when there is no sterilant flow betweenthe two chambers. The two chambers are still independently operable. Oneof the advantages of the arrangement is that devices with greater lengthsuch as device 44 can be accommodated in the space between chamber 2 andchamber 4.

[0067] Chambers 2 and 4 share the top surface and the bottom surface,and are equipped with two sealable doors. Chamber 2 has a large door onthe top surface and chamber 4 has a smaller door on the upper surface.The smaller door is in the large door, but the two doors can be operatedindependently.

[0068]FIG. 4 shows an apparatus of the present invention similar to thatshown in FIG. 3. The difference between the two embodiments shown inFIG. 3 and FIG. 4 is that in the apparatus of FIG. 4 chamber 2 andchamber 4 are in fluid communication through a lumen device 40.Therefore, this apparatus has all the advantages possessed by theapparatus of FIG. 3. In addition, it can be used to effectivelysterilize devices with long narrow lumens. In this case, a removableinterface 6 a with an opening 7 is provided to accommodate the lumendevice 40. The interface 6 a can be installed in a similar way asdiscussed and shown in FIG. 1A. Valves 19 a and 19 b can be providedbetween pump 18 and the chambers.

[0069]FIG. 5 demonstrates the use of a container 20 in the chambers 2and 4. For certain devices the sterility needs to be maintained afterthe sterilization. A sterilant vapor-permeable andmicroorganism-impermeable container is usually used to achieve the goalto keep the microorganism away form the sterilized devices after thedevices have been sterilized. As shown in FIG. 5, a container 20 isplaced in either chamber 2 or chamber 4, or both. The rest of the systemis the same as the apparatus shown in FIG. 1. The container is providedwith a membrane (not shown) which is sterilant vapor-permeable andmicroorganism-impermeable and can be located at any convenient positionon the wall of the container 20. The sterilant vapor-permeable andmicroorganism-impermeable membrane can be made of any conventionalmaterial known the art such as TYVEK™ nonwoven polyethylene fabric,nonwoven polypropylene such as SPUNGUARD™ , or similar material. Duringa sterilization process, the sterilant vapor generated from a liquidsterilant in chamber 2 or 4 penetrates into the container 20 through themembrane and sterilizes the device placed inside the container 20. Thedevices to be sterilized can also be pretreated with liquid sterilantand then the liquid sterilant contained or absorbed by the devices isvaporized under vacuum applied through vacuum pump 16. Another option isto provide the container 20 with liquid sterilant before thesterilization process starts, then close a sealable door of thecontainer 20, and apply vacuum to the container 20 to vaporized theliquid sterilant contained in the container 20. When the sterilizationcycle is complete, the container is removed from the chamber. Because ofthe microorganism-impermeable feature, the container 20 can maintain thesterility of the device inside the container 20. This greatly reducesthe chance of re-contamination during the handling of the sterilizeddevice.

[0070]FIG. 6B shows a sterilization apparatus similar to that of FIG. 5.In the apparatus shown in FIG. 6B, a container 22 for lumen device 40 isplaced across opening 7 b in the interface 6 c. The opening 7 b issealed around the outside of the container 22, for example, by an O-ringor other similar material mounted in the opening 7 b. Container 22 alsohas an interface 22 a with an opening 22 b as shown in FIG. 6A. Theopening 22 b is also sealed around the outer surface of the, lumendevice 40 so that no gas or vapor can flow therebetween when the seal isin gas-tight seal state. When desirable, the sealing between the outersurface of the lumen device 40 and the opening 22 b of the interface 22a of the container 22 can be released so that the outer surface of thelumen device 40 adjacent the sealing is sterilized. A sterilantvapor-permeable and gas-permeable, but microorganism-impermeablemembrane 24 is provided to both portions of the container 22 in chamber2 and 4. The membrane 24 can be located at any convenient position oncontainer 22, such as at both ends of the container 22. Throughmembranes 24 and lumen 42 of the lumen device 40, chamber 2 and chamber4 are placed in fluid communication. By applying vacuum to eitherchamber with vacuum pump 16, a pressure differential can be establishedand a flow of sterilant is generated between the two chambers. Thecontainer 22 serves to maintain the sterility of the lumen device 40placed therein following the sterilization.

[0071]FIG. 7 shows a sterilization apparatus which comprises a container26. The container 26 is divided by an interface 6 d. Like interface 6 adescribed FIG. 2, interface 6 d is sealable and has an opening 7 c.Container 26 is accessible to sterilant source 12 or enclosure 10. Thegap between the inner surface of chambers 2 and 4 and the outer surfaceof the container 26 is gas-tight sealed so that no air or sterilantvapor can flow through the gap form chamber 2 to chamber 4 or viceversa. In the embodiment shown in FIG. 7, the sealing of the gap betweenthe inner surface of chambers 2 and 4 and the outer surface of thecontainer 26 is provided at the about same location where the interface6 d separates the container 26 into two portions. The two portions ofthe container 26 separated by the interface 6 d are in fluidcommunication through the lumen 42. The opening 7 c is sealed around theouter surface of the lumen device 40 in the same manner as described inthe section for the apparatus shown in FIG. 2. A sterilantvapor-permeable and gas-permeable, but microorganism-impermeablemembrane is provided at both portions of the container 26. Thus, apressure differential can be generated between the two chambers andbetween the two portions of the container 26 by means of vacuum pump 16and/or pump 18. The pressure difference between the two portions of thecontainer 26 forces sterilant fluid to flow through the lumen 42, andboth the interior and the exterior of the lumen device 40 and otherdevices in the container 26 are efficiently sterilized. The sterility ofthe devices in the container 26 is maintained following thesterilization.

[0072] The present invention is described based on drawings anddifferent embodiments. It is obvious to one of ordinary skill in the artthat various modifications can be made without departing from the spiritand the scope of the present invention.

What is claimed is:
 1. An apparatus for treating a lumen device, thelumen device having a lumen therethrough, the lumen having a first endand a second end, the apparatus comprising: a container with at leastone interface, wherein the at least one interface in the containerseparates the container into at least a first compartment and a secondcompartment; the interface having an opening therethrough to receive thelumen device with the first end of the lumen in the first compartmentand the second end of the lumen in the second compartment; and a sourceof germicide in fluid communication with the container, wherein thegermicide is in aerosol form.
 2. An apparatus according to claim 1further comprising means for creating a pressure differential betweenthe first chamber and the second chamber whereby to induce a flow of thegermicide from the first chamber toward the second chamber through thelumen.
 3. An apparatus according to claim 2 wherein the means forcreating a pressure differential between the first chamber and thesecond chamber comprises a vacuum pump connected to the second chamber.4. An apparatus according to claim 2 wherein the means for creating apressure differential between the first chamber and the second chambercomprises a pump connected to the first chamber and to the secondchamber.
 5. An apparatus according to claim 1 wherein the germicidecomprises hydrogen peroxide.
 6. An apparatus according to claim 1wherein the interface is adapted to seal around the lumen device.
 7. Amethod for treating a lumen device, the lumen device having a lumentherethrough, the lumen having a first end and a second end, the methodcomprising: providing a container with at least one interface, whereinthe at least one interface separates the container into at least a firstcompartment and a second compartment; placing the lumen device incontainer extending across the at least one interface, wherein the firstend is in the first compartment and the second end is in the secondcompartment; and introducing a germicide in aerosol form into the firstcompartment; and flowing the germicide from the first compartmentthrough the lumen into the second compartment.
 8. A method according toclaim 7 wherein the germicide is flowed from the first chamber towardthe second chamber through the lumen by creating a pressure differentialbetween the first chamber and the second chamber.
 9. A method accordingto claim 8 wherein the pressure differential between the first chamberand the second chamber is created by lowering the pressure in the secondchamber with a vacuum pump.
 10. A method according to claim 8 whereinthe pressure differential between the first chamber and the secondchamber is created by pumping atmosphere from the second chamber intothe first chamber.
 11. A method according to claim 7 wherein thegermicide comprises hydrogen peroxide.
 12. A method according to claim 7and further comprising the step of sealing the interface around thelumen device.